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| Article Authors: | R Mallone; M Scotto; C N Janicki; E A James; L Fitzgerald-Miller; R Wagner; P Gottlieb; J Thorpe; N Jospe; I Durinovic-Bellò; C Boitard; O Lou; C M Dayan; F S Wong; T-Cell Workshop Committee, Immunology of Diabetes Society |
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| Article Title: | Immunology of Diabetes Society T-Cell Workshop: HLA class I tetramer-directed epitope validation initiative T-Cell Workshop Report-HLA Class I Tetramer Validation Initiative. |
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| Reference ID: | 1022561 |
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| Abstract: | BACKGROUND: Identification of T-cell reactivity to β-cell antigen epitopes is an important goal for studying pathogenesis and for designing and monitoring of immunotherapeutic interventions in type 1 diabetes (T1D). METHODS: We performed a multicentre validation of known human leukocyte antigen (HLA) class I CD8+ T-cell epitopes. To this end, peripheral blood T-cell responses were measured in 35 recently (<2 years) diagnosed HLA-A*02:01+ T1D patients using blind-coded HLA-A2 tetramers (TMrs) and pentamers (PMrs), encompassing two epitopes of preproinsulin (PPI; PPI$\def\endash{\hbox{--}} _{\rm{A12\endash 20}}$ and PPI$\def\endash{\hbox{--}} _{\rm{B10\endash 18}}$) and two epitopes of glutamic acid decarboxylase (GAD; GAD(114-122) and GAD(536-545) ). We also compared the readout of TMrs and PMrs with a CD8+ T-cell interferon-γ enzyme-linked immunospot assay. RESULTS: Despite the minute frequencies of autoreactive cells detected by TMrs/PMrs, most (73-77%) T1D patients had responses to one or more of the epitopes used. All four epitopes were recognized by T1D patients, with a prevalence ranging from 5 to 25%. TMrs and PMrs detected more positive responses to the β-cell epitopes than CD8+ T-cell interferon-γ enzyme-linked immunospot. However, concordance between positive responses to TMrs and PMrs was limited. CONCLUSIONS: Using a multicentre blind-coded setup and three different T-cell assays, we have validated PPI and GAD epitopes as commonly recognized CD8+ T-cell targets in recently diagnosed T1D patients. Both TMrs and PMrs showed higher detection sensitivity than the CD8+ T-cell interferon-γ enzyme-linked immunospot assay. However, there are some important methodological issues that need to be addressed in using these sensitive techniques for detecting low frequency responses. Copyright © 2011 John Wiley & Sons, Ltd. |
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| Affiliations: | INSERM U986, DeAR Lab Avenir, Saint Vincent de Paul Hospital, Paris, France; Paris Descartes University, Paris, France; Assistance Publique Hôpitaux de Paris, Hôtel Dieu, Department of Diabetology, Paris, France. Roberto.Mallone@inserm.fr. |
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| Date: | 2011 |
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| Reference Type: | Literature |
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| PubMed ID: | 22069251 |
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| Journal: | Diabetes Metab Res Rev |
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| Journal Volume: | 27 |
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| Article Pages: | 720-6 |
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| Journal ISSN: | 1520-7560 |
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| Curation Last Updated: | 2011-12-05 20:01:41 |
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